tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibitor plus tyrosine kinase inhibitor with or without transarterial chemoembolization for unresectable hepatocellular carcinoma.
Authors: Hongyu Pan, Minghao Ruan, Riming Jin, Jin Zhang, Yao Li, Dong Wu, Wen Sun, Ruoyu Wang
Journal: Journal of Clinical Oncology (2023)

e16123 Background: Transcatheter arterial chemoembolization (TACE) has been combined with immune checkpoint inhibitor (ICI)-based systematic therapies for unresectable HCC (uHCC) with promising efficacy. However, whether the addition of TACE to the combination of ICI and tyrosine kinase inhibitor (TKI) (ICI+TKI+TACE) is superior to ICI+TKI combination therapy is still not clear. Thus, this study compares the efficacy of ICI+TKI+TACE triple therapy and ICI+TKI doublet therapy in patients with uHCC. Methods: uHCC patients treated with either ICI+TKI+TACE triple therapy or ICI+TKI doublet therapy were retrospectively recruited between January 2016 and December 2021 at Eastern Hepatobiliary Surgery Hospital. The patients from ICI+TKI+TACE group and ICI+TKI group were further subjected to propensity score matching based on the baseline characteristics. The primary outcome was progression-free survival (PFS) in matched patients. The secondary outcomes were overall survival (OS) and objective response rate (ORR). Post-progression survival (PPS) as well as treatment-related adverse events (TRAEs) were also assessed. Results: A total of 120 patients were matched. The median PFS was 8.4 months in ICI+TKI+TACE triple therapy group versus 6.6 months in ICI+TKI doublet therapy group (HR 0.72, 95%CI 0.48-1.08; p=0.115). Similar results were obtained in term of OS (26.9 versus 24.2 months, HR 0.88, 95% CI 0.51-1.52; p=0.670). The ORR in the triple therapy group was comparable with that in the doublet therapy group (16.6% versus 21.6%, p=0.487). Further subgroup analysis for PFS illustrated that patients without previous locoregional treatment (preLRT) (10.5 versus 3.7 months, HR 0.35 [0.16-0.76]; p=0.009), without previous treatment (10.5 versus 3.5 months, HR 0.34 [0.14-0.81]; p=0.015) or treated with lenvatinib (14.8 versus 6.9 months, HR 0.52 [0.31-0.87]; p=0.013) can significantly benefit from triple therapy compared with doublet therapy. A remarkable interaction between treatment and preLRT ( p=0.049) or TKIs-combined ( p=0.005) was also detected in term of PFS. Kaplan-Meier analysis of PPS revealed that patients with post progression treatment displayed significant improved survival in both ICI+TKI+TACE and ICI+TKI groups. The incidence of TRAEs was comparable between two groups. Conclusions: In selected uHCC patients (without preLRT or treated with lenvatinib as combination), the addition of TACE to ICI+TKI combination therapy can remarkably improve PFS.
Development of natural language processing (NLP) models for extracting key features from unstructured notes to create real-world data (RWD) assets for clinical research at scale.
Authors: Smita Agrawal, Rohini George, Vivek Prabhakar Vaidya, Sangavai Chakkrapani, Rambaksh Prajapati, Srikanth Tankala, Dhaval Parmar, Vinay Phani Santosh Lakkimsetty, Tapasya Bhardwaj, Ashwani Ashwani, Emma Mendonca, Babu Narayanan, Krishna Kumar Swaminathan, Pranay Mukherjee
Journal: Journal of Clinical Oncology (2023)

6607 Background: RWD derived from Electronic Health Records (EHR) has detailed clinical information about patient journeys that can assist in clinical research, trial design, safety assessments etc. However, much of the vital information is locked away in unstructured clinical texts and needs to be converted to structured format to be useful for downstream applications. We demonstrate how this can be achieved at scale with a high degree of accuracy through NLP. Methods: NLP models were developed to extract data for 11 clinical variables from unstructured notes of ~98k lung cancer patients and merged with the structured data into a common data model (Table). These models were a combination of domain knowledge, rule-based models, machine learning models, and deep learning models. The increase in fill rate per variable over structured data only was used to quantify the improvement by NLP. The accuracy of the models was assessed against a manually curated dataset comprising of 752 patients. Results: The NLP models significantly improved the fill rate of key clinical variables and were able to extract the information from clinical notes with high accuracy (Table). For some variables such as NSCLC/SCLC status, surgery, tumor grade and histology, all or most of the data was extracted via NLP. Metastatic status via NLP included distant metastasis, locally advanced disease and no metastasis whereas in the structured data, only data for distant metastasis was present. In the case of Performance Status (PS), even though a significant number of patients had at least 1 PS recorded in the structured data, NLP significantly increased longitudinal capture, thus increasing the density of this variable per patient. Conclusions: NLP models can be developed and used to enrich structured RWD data by extracting information from unstructured documents thus significantly improving the utility of this data for downstream applications. Given the high accuracy of these models and the scale at which they can be run, this can be a good alternative to human curation or can augment human curation enabling the creation of very large-scale datasets for clinical research. [Table: see text]
Tislelizumab in combination with gemcitabine plus cisplatin as neoadjuvant therapy for lymph node‐positive bladder cancer.
Authors: Xiao Yang, Qiang Cao, Pengchao Li, Lingkai Cai, Juntao Zhuang, Qiang Lyu
Journal: Journal of Clinical Oncology (2023)

e16599 Background: Although multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs combined with gemcitabine plus cisplatin in MIBC, lymph node‐positive bladder cancer is generally excluded. Our specific aim was to compare the efficacy and prognosis of neoadjuvant tislelizumab combined with gemcitabine plus cisplatin in patients with lymph node‐positive bladder cancer. Methods: In this single arm phase II study, eligible patients had cT2-T4a N+ M0 MIBC, cisplatin-eligible, and to be planned radical cystectomy (RC). Patients received tislelizumab 200 mg in day D8, cisplatin 70 mg/m 2 D2, and gemcitabine 1000 mg/m 2 D1 and D8 every 21 days for 3 or 4 cycles. RC was performed within 6 weeks after last dose treatment. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging ( &lt; ypT2), EFS, OS and safety. Results: By Jan 2023, 17 eligible pts (2cT2, 10 cT3, 5 cT4) were enrolled. 14 pts have completed neoadjuvant therapy, with median age of 67 (60-81) years, among whom 10 pts underwent RC and two declined RC. According to RECIST 1.1, 6 pts achieved a clinical complete response (cCR)(6/14,42.8%). Pathological results revealed 5 pCR (ypT0N0, 50%), 3 ypT1N0, and 2 ypT2/T3N0. A complete nodal response (pN0) occurred in 10 (100%) pts post- tislelizumab +chemotherapy and 8 ( &lt; ypT2N0,80%) pts achieved pathologic downstaging. Most common neoadjuvant therapy related AEs of any grade were hematologic toxicities (11/14,78.5%), nausea (9/14,64.2%), vomiting (8/14,57.1%), decreased appetite (6/14,42.8%), fatigue (4/14,28.5%), pruritus (3/14,21.4%) and ALT/AST increased (4/14,28.5%). Grade ≥3 neoadjuvant therapy related AEs were neutropenia (n = 3), thrombocytopenia (n = 2), anemia (n = 2). One patient discontinued GC plus tislelizumab due to AEs. Conclusions: Patients with clinically lymph node‐positive bladder cancer have significant pN0 after neoadjuvant therapy. Neoadjuvant tislelizumab plus gemcitabine/cisplatin was feasible and provided meaningful pathologic responses in lymph node‐positive bladder cancer. Clinical trial information: NCT04570410 .
Construction of DNA methylation-based biomarkers for diagnosis of hepatocellular carcinoma.
Authors: Ximing Xu, Jiayu Chen, Yang Shen
Journal: Journal of Clinical Oncology (2023)

3048 Background: Hepatocellular carcinoma is the most common malignant tumor in China. Most of the patients are found in the advanced stage, which causes its low survival rate. According to the latest epidemiological data, hepatocellular carcinoma is the second leading cause of cancer mortality. DNA methylation is closely related to tumor development. In this study, differentially expressed methylated genes related to tumorigenesis and development were screened from the database and the diagnostic model was constructed for early screening. Methods: Limma package was used to analyze the differences between TCGA _ LIHC liver cancer and GSE113409 normal blood methylation sites and differentially expressed methylation sites (logFC&gt;1，p&lt;0.05) were identified. The TCGA _ LIHC methylation database was used as the training set. Lasso method, and random forest method were used for screening the differentially expressed methylation sites for the construction of the diagnostic model. After that, the characteristic coefficient of methylation sites and ROC curve of the diagnostic model were obtained from the training set. According to the cd-score, HCC patients could be diagnosed in the early stage, thus improved their survival. Results: Limma package was used to analyze the differences between TCGA _ LIHC liver cancer and GSE113409 normal blood methylation sites and 7109 differentially expressed methylation sites (logFC&gt;1，p&lt;0.05) were identified. Then the top 1000 differentially expressed methylation sites were selected. The TCGA _ LIHC methylation database was used as the training set. 30 methylation sites were screened by lasso method, and 20 methylation sites were screened by random forest. Taking the intersection, a total of 6 methylation sites were obtained for diagnostic model: cg00346208, cg00084798, cg00458878, cg00006397, cg00325910, cg00399027. The characteristic coefficient of methylation sites were displayed in the table below and the AUC of the diagnostic model was 0.9991579. High cd-score tended to have hepatocellular carcinoma, and vice versa. Conclusions: We have identified several DNA methylation markers for the diagnosis of hepatocellular carcinoma from GEO and TCGA databases. This model can predict hepatocellular carcinoma and the AUC is higher than that of AFP, which means it may become a more sensitive indicator for the diagnosis of liver cancer. [Table: see text]
Effect on in-hospital outcomes of patients with hepatocellular carcinoma on aspirin.
Authors: Armaan Dhaliwal, Aalam Sohal, Hunza Chaudhry, Ishandeep Singh, Raghav Sharma, Dino Dukovic, Shivam Kalra, Kirti Arora, Kanwal Bains, Ponnandai Sadasivan Somasundar
Journal: Journal of Clinical Oncology (2023)

e16162 Background: Despite the use of new immunotherapies, hepatocellular carcinoma (HCC) has a poor survival rate. Through multiple molecular mechanisms, aspirin (ASA) has demonstrated a reduced incidence of HCC, however, the impact of long-term aspirin use on in-hospital outcomes has not been studied. Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 to identify patients with HCC. Patients were stratified into two groups, based on long-term aspirin use. Information was collected regarding patient demographics, Elixhauser comorbidities, interventions, etiology and decompensations of the liver disease. Outcomes studied included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The association between long-term aspirin use and outcomes was studied using multivariate analysis. Results: 224,735 patients were included in the study. Of them, 18,835 (8.4%) patients were on long-term aspirin. The majority of the patients with ASA use were White (61.3%), men (78.2%), and aged &gt; 65 years old (68.8%). Patients in the ASA group had a higher incidence of NASH and decreased rates of hepatic decompensation than those not on ASA. Patients with aspirin use had lower incidence of sepsis (2.76% vs 3.54%), shock (4.86% vs 8.23%), AKI (30.9% vs 33.4%), ICU admission (3.88% vs 7.4%) and in-hospital mortality (5.18% vs 9.87%). After adjusting for confounding factors, ASA use was associated with a 30% lower risk of in-hospital mortality (aOR-0.70, 95% CI-0.60-0.82, p&lt;0.001). ASA users also had a 21% lower odds of developing shock (aOR-0.79, 95% CI-0.67-0.94, p-0.007) and 31% lower odds of requiring ICU admission (aOR-0.69, 95% CI-0.54-0.78, p&lt;0.001). No statistically significant difference was noted in the risk of sepsis and AKI between the two groups. Conclusions: Our study noted that patients on long-term aspirin use had better in-hospital outcomes such as mortality, shock and ICU admissions compared to non-aspirin users. These findings are of interest, and further randomized clinical trials confirming the benefits of aspirin in improving outcomes in HCC patients need to be conducted. [Table: see text]
Real world impact of hepatocellular carcinoma stage and hepatic function on health-related quality of life.
Authors: Amol Gupta, Jane Zorzi, Won Jin Ho, Marina Baretti, Nilofer Saba Azad, Paige Griffith, Doan Dao, Amy K. Kim, Benjamin Philosophe, Christos Georgiades, Ihab R. Kamel, Richard Burkhart, Robert Liddell, Kelvin Hong, Christopher Shubert, Kelly Lafaro, Jeffrey Meyer, Robert A. Anders, William Burns, Mark Yarchoan
Journal: Journal of Clinical Oncology (2023)

e16215 Background: Health-Related Quality of Life (HRQoL) is an important prognostic indicator and clinical endpoint for patients with hepatocellular carcinoma (HCC). The relationship between cancer stage, liver function, performance status, and HRQoL in HCC in a real-world clinical setting is not well defined. Methods: A retrospective chart review was undertaken of consecutive patients with HCC treated at our institution's liver multidisciplinary clinic between February 2020 and August 2022. We examined the relationship between Barcelona Clinic Liver Cancer (BCLC) stage, Child Pugh (CP) score, and Eastern Cooperative Oncology Group (ECOG) performance status on HRQoL at diagnosis. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Results: Fifty-one patients met our inclusion criteria. The median age was 69 and the mean FACT-Hep score was 130.3 ± 20.3. FACT-Hep total and subscales showed no significant association with BCLC stages A, B, and C (p =0.224), except in the Emotional Well Being (EWB) subscale (p =0.001). There was no impact of ECOG performance status on the FACT-Hep scores, except for the Functional Well Being (FWB) subscale (p=0.006). Patients with a CP B had significantly more impairment in FACT-Hep than patients with CP A, including FACT-Hep total score (118.5 ±27.3 versus 134.3 ±23.8; p =0.021) and subscales including the Physical Well Being (p =0.018), FWB (p =0.030), Hepatobiliary Cancer Subscale (p &lt;0.001), and FACT-Hep Trial Outcome Index score (p =0.003). Conclusions: Cancer stage poorly correlates with HRQoL at diagnosis in HCC patients. Impaired liver function reduces overall quality of life in HCC patients. Further large-scale prospective studies should be undertaken which incorporate validated HRQoL tools in the routine assessment of HCC patients. [Table: see text]
Longitudinal variability in symptom burden for patients with prostate cancer (PC).
Authors: Risa Liang Wong, Heather H. Cheng, Jesse R. Fann, James Hnida, Marty Chakoian, Samia Jannat, Yael Schenker, Evan Y. Yu, John L. Gore
Journal: Journal of Clinical Oncology (2023)

e17019 Background: Patients with PC often live for many years and can experience burdensome symptoms associated with PC and its treatment. The longitudinal fluctuations in symptom burden for a given individual with PC, or for groups with different PC disease states, are not well-described. We assessed self-rated performance status (PS), pain interference with daily activities, bother from sexual dysfunction, depression, and anxiety symptoms longitudinally for a cohort of patients with PC. Methods: For one year, patients with PC and ≥1 Urology or Medical Oncology clinic visit in the prior 6 months were emailed surveys every 60 days containing the ECOG PS instrument (range 0-4, higher scores = worse PS), PROMIS Pain Interference Short Form 4a (normalized range 1-5, higher scores = greater pain interference), PROMIS Sexual Bother (Male) items SFBOT 204, 205, and 206 (normalized range 1-5, higher scores = greater bother), PHQ-9 depression scale (range 0-27, score ≥10 considered positive for moderate symptoms), and GAD-7 anxiety scale (range 0-21, score ≥10 considered positive for moderate symptoms). We used chart review to obtain baseline characteristics and one-way ANOVA for comparisons. Results: For 201 enrolled patients, mean (SD) number of surveys completed was 5.8 (1.8) over a mean (SD) of 10.6 (3.1) months. At baseline, 50.7% had localized PC (LPC), 18.9% biochemically recurrent PC (BCR-PC), and 30.3% metastatic PC (MPC). 40.8% of patients were on androgen deprivation therapy, which was not associated with greater sexual bother (p = 0.17). Mean (SD) values for ECOG PS, pain interference, sexual bother, the PHQ-9, and the GAD-7 are shown by PC disease state (Table). For patients who completed ≥2 surveys (N = 192), mean (SD) ranges for these scales were 0.4 (0.6), 0.8 (0.9), 1.2 (0.8), 3.7 (3.3), and 2.6 (2.6), respectively. Mean range differed by PC disease state for ECOG PS (0.31 LPC vs 0.63 BCR-PC vs 0.59 MPC, p = 0.003) and pain interference (0.63 LPC vs 1.02 BCR-PC vs 0.95 MPC, p = 0.03). For patients with ≥1 positive PHQ-9 (N = 36) or GAD-7 (N = 11) screen over ≥2 surveys, a mean (SD) of 41% (30%) and 39% (33%), respectively, of their total screens were positive. Mean (SD) ranges for these patients were 8.4 (3.6) for the PHQ-9 and 8.5 (3.4) for the GAD-7 (both p &lt; 0.001 compared with those who never screened positive). Conclusions: Patients with more advanced PC had worse PS, pain, and depression, but those with BCR-PC reported greater longitudinal fluctuations in PS and pain. Patients who screened positive for depression or anxiety only did so in ~40% of their surveys, and had greater longitudinal variability in their PHQ-9/GAD-7 scores than those who never screened positive. [Table: see text]
A randomized phase II study comparing single-agent olaparib, single-agent cediranib, and the combinations of cediranib/olaparib, olaparib/durvalumab (MEDI4736), cediranib/durvalumab (MEDI4736), and olaparib/AZD5363 (capivasertib) in women with recurrent, persistent, or metastatic endometrial cancer.
Authors: B.J. Rimel, David Bender, Danielle Enserro, Shannon Neville Westin, Debra L. Richardson, Laura L. Holman, Nitya Alluri, Ashley Stuckey, Ruchi Garg, Sarah Gill, Edward Tanner, Charles A. Leath, Floor Jenniskens Backes, Aimee Fleury, Helen Mackay
Journal: Journal of Clinical Oncology (2023)

TPS5629 Background: Identifying new approaches for the treatment of advanced endometrial cancer (EC) is a priority. A platform study design allows for a faster investigation of novel drug combinations. NRG-GY012 is an ongoing platform study investigating drug combinations with the PARP inhibitor olaparib (O) and the anti-angiogenic agent cediranib (C). Results from the first set of arms established improved PFS for combination cediranib/olaparib over C alone, but did not meet its prespecified statistical significance. In this second set of arms, based on preclinical data, we are investigating the combination of O with an AKT inhibitor (capivasertib), O with durvalumab and C with durvalumab compared to the reference arm of C alone. Methods: This is a multicenter randomized four arm study for patients with recurrent, metastatic or persistent EC. Patients are randomized 1:1:1:1 to cediranib PO 30 mg Daily; olaparib 300 mg PO BID and capivasertib 400mg 4 day on/3 off schedule; olaparib 300 mg PO BID and durvalumab 1500mg q28 days; or the combination of cediranib 20 mg PO Daily 5 days on/2 days and durvalumab 1500mg q28. All treatment cycles are 28 days. Primary endpoint is progression free survival (PFS). The study is powered to detect a doubling in median PFS from 3.6 (based on cediranib alone) to 7.2 months with 90% power, using a one-sided test with α = 0.05 per comparison. Forty patients will be enrolled per arm, with an interim futility analysis planned at 50% information time. Eligibility includes endometroid, serous, and mixed histology EC; at least 1 prior line of chemotherapy (no more than 2 lines for metastatic disease), prior endocrine or immunotherapy alone is allowed; prior treatment with lenvatinib and pembrolizumab is excluded. Archival tumor tissue and blood samples are being collected for translational studies. The study is open across the NRG network; 76 of a planned 168 patients are enrolled to date. Safety analysis at the time of 36 patients enrolled did not demonstrate any new safety signals and the study was approved to continue enrollment. Clinical trial information: NCT03660826 .
Impact of obesity on admissions for COVID-19 with concurrent prostate cancer.
Authors: Renuka Verma, Kamleshun Ramphul, Mehndi Dandwani, Shivani Sharma, Suma Sri Chennapragada, Alekhya Pagidipally, Shaheen Sombans, Sailaja Sanikommu, Yogeshwaree Ramphul, Stephanie G Mejias, Prince Kwabla Pekyi-Boateng, Fnu Arti, Balkiranjit Kaur Dhillon, Vijay Kumar, Petras Lohana
Journal: Journal of Clinical Oncology (2023)

e17110 Background: Obesity is a significant risk factor for prostate cancer and its associated mortality. Recent studies have shown that a five-point rise in BMI can lead to a 10% rise in death among these patients. Since the pandemic of COVID-19, obesity has also been associated with poorer outcomes among the general population. As there is a paucity of data on the impact of obesity among prostate cancer admissions with COVID-19, we conducted a retrospective study to provide a novel perspective. Methods: Patients with a diagnosis of COVID-19 were used for our study from the 2020 National Inpatient Sample. We included cases between April 2020 to December 2020. Hospitalization records with prostate cancer and obesity were also identified via their respective ICD-10 codes. The differences in outcomes, including non-invasive ventilation, use of mechanical ventilation, pulmonary embolism, events of Acute Kidney Injury(AKI) and in-hospital mortality were compared between obese and non-obese patients with a history of prostate cancer, admitted for COVID-19. We also compared the mean lengths of stay, mean ages between the two groups, and their overall mean hospitalization charge. Results: A total of 7165 prostate cancer patients were hospitalized with COVID-19 between 1st April 2020 to 31st December 2020 in the United States. 1065 (14.9%) were obese. Prostate cancer patients admitted with COVID-19 who were obese were also younger (mean age 71.75 years) than those who were not obese (77.50 years) and recorded a more extended stay (mean LOS 9.68 days vs. 7.93 days). Obese patients also recorded a higher adjusted odds ratio for needing non-invasive ventilation (aOR 1.736, 95% CI 1.331-2.263, p &lt; 0.01), mechanical ventilation (aOR 1.894, 95% CI 1.533-2.340, p &lt; 0.01), events of acute kidney injury (aOR 1.328, 95% CI 1.137-1.550, p &lt; 0.01), and in-hospital mortality (aOR 1.246, 95% CI 1.033-1.502, p = 0.021). While more patients with obesity developed pulmonary embolism (4.2% vs. 3.6%) after adjusting for confounders, the result was not statistically significant (aOR 1.258, 95% CI 0.879-1.800, p = 0.209). Obese patients also recorded a higher mean hospital charge compared to non-obese cases ($117200.50 vs. $81028.15). Conclusions: Obesity in prostate cancer patients admitted with COVID-19 is linked with several poor outcomes and complications, including AKI, mechanical ventilation, non-invasive ventilation, and mortality. Thus, physicians must identify such cases as higher-risk and encourage closer monitoring during their hospitalizations.